Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the neonatal rat spinal cord slice preparation responses of the dorsal horn interneurons to iontophoretic or bath application of methionine-enkephalin (ME), substance P (SP) and somatostatin (SS) were qualitatively similar to those obtained in intact spinal cord. Thus, SP powerfully excited almost all neurons tested (15/16), while ME and SS depressed neuronal discharges in 13/14 and 4/6 units respectively. In some dorsal horn neurons the iontophoretic application of ME caused a marked depression of the SP-induced excitation. Angiotensin II (AgII) had no effect on dorsal horn units (n = 8). In the slices perfused with a Ca2+-free, Mg2+-high Krebs solution the extracellularly recorded effects of ME, SP and SS were not significantly modified, suggesting that the peptides were acting directly on postsynaptic sites. The results also indicate that the in vitro rat spinal cord slice preparation can be successfully utilized for further studies on the cellular mechanisms of actions of neuropeptides, particularly in relation to synaptic transmission processes in the dorsal horn.
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PMID:Neonatal rat spinal cord slice preparation: postsynaptic effects of neuropeptides on dorsal horn neurons. 616 14

1. The transient release of 86Rb from parotid slices induced by secretagogues was investigated. 2. In the absence of external Ca, only one transient response (to carbachol) could be obtained. 3. After blocking the cholinergic stimulus with atropine, a second response (to substance P) could be elicited if the slices were briefly (2 min) exposed to a Ca-containing medium. 4. The magnitude of the substance P response depended on the concentration of Ca to which the slices had been exposed. 5. An exposure to Ca of 2 min duration was found to be sufficient to restore maximal substance P responsiveness. 6. These results are interpreted to mean that the cholinergic stimulus elicited a transient 86Rb efflux response by first releasing a finite pool of cellular Ca which could be reloaded from the extracellular space by a brief (2 min) incubation in a Ca-containing medium. The magnitude of the subsequent response to substance P apparently reflects the quantity of Ca taken up by the pool. 7. A number of cationic substances antagonized the restoration by Ca of the substance P response; the rank order of potency was: La3+ = Tm3+ greater than Co2+ = Ni2+ greater than neomycin much greater than Mg2+. 8. These same substances were examined for their relative abilities to inhibit Ca binding to phosphatidylinositol-4, 5-bisphosphate; in this case the rank order of potency was: La3+ = Tm3+ greater than neomycin greater than Co2+ greater than Ni2+ = Mg2+. 9. It is concluded that the uptake process does not appear to reflect Ca binding to phosphatidylinositol-4, 5-bisphosphate.
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PMID:Nature of the receptor-regulated calcium pool in the rat parotid gland. 618 69

With appropriate measures to protect 3H-substance P (3H-SP) from proteolytic degradation and from nonspecific adsorption to glass-fiber filters, we have been able to demonstrate reliably a high-affinity specific binding of 3H-SP to rat submaxillary/sublingual gland membranes with a KD of 1 nM and Bmax of 6 pmoles/g of tissue. The relative potencies of various SP fragments and related analogues in reducing 3H-SP binding parallel their potencies in stimulating phosphatidylinositol turnover, amylase release, and salivation, thus supporting an association of the observed 3H-SP binding site with the physiological SP receptors in this tissue. This binding is selectively stimulated by some divalent cations (Mn2+ greater than Mg2+ greater than Ca2+) but inhibited by several guanyl nucleotides, suggesting a possible linkage to adenylate cyclase. However, no effect of SP on either the basal or the norepinephrine-stimulated adenylate cyclase activity could be demonstrated in salivary gland homogenates.
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PMID:3h-substance P binding to salivary gland membranes. Regulation by guanyl nucleotides and divalent cations. 619 Nov 91

Histamine secretion was induced by substance P, in a dose-dependent manner, from rat peritoneal mast cells, both in the presence and absence of Ca2+ in the medium, and disodium cromoglycate (DSCG) produced a dose-dependent inhibition of the histamine secretion in Ca2+-containing medium. However, in the absence of Ca2+, DSCG was ineffective or had a far weaker activity. Mg2+, Sr2+ and Ba2+ were ineffective in restoring the DSCG activity when added to medium devoid of divalent metal ions. Therefore, extracellular Ca2+ seems to be a specific requirement for the binding of DSCG to its "receptors" on the mast cell surface or some steps in the DSCG action.
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PMID:Disodium cromoglycate inhibition of substance P-induced histamine secretion is calcium dependent. 619 41

Rohon-Beard neurones show substance P-like immunoactivity in their somas and in their centrally projecting axons. Peripherally, the morphology of their free nerve endings within the trunk skin has been shown using horseradish peroxidase staining. The excitation of Rohon-Beard neurones by natural and electrical stimulation of the skin has been examined using intracellular micro-electrodes in the late embryo of Xenopus laevis. Rohon-Beard cells are sensitive to transient, local indentation of the trunk skin, responding with one or a few impulses. They adapt rapidly to repeated stimulation. They can also be excited by a brief current pulse to the skin. They are not sensitive to slow indentation of the skin, nor are they excited by epithelial action potentials. The responses to skin stimulation are not abolished by a Ringer solution containing 12 mM-Mg2+ and only 0.5 mM-Ca2+. Intracellularly evoked action potentials in single Rohon-Beard cells are sometimes sufficient to evoke sustained episodes of fictive swimming. The results indicate that Rohon-Beard cells are responsible for detecting light touch stimuli to the embryo's body and for initiating swimming in response to this stimulus.
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PMID:Sensory physiology, anatomy and immunohistochemistry of Rohon-Beard neurones in embryos of Xenopus laevis. 620 12

Spontaneous dorsal root potentials (sDRPs) were recorded from the dorsal roots of the isolated frog spinal cord using sucrose gap techniques. sDRPs were always negative (depolarizing) in sign and ranged in size from about 100 microV to 6.0 mV. The largest sDRPs were 25-40% of the amplitude of DRPs evoked by stimulation of adjacent dorsal roots. Hypoxia or accumulation of extracellular K+ ions did not appear responsible for the generation of this spontaneous activity since exposing the cord to unoxygenated Ringer's solution decreased sDRPs and K+-sensitive microelectrodes indicated that only small changes in extracellular K+ (approximately 0.15 mM) were produced coincidently with the largest sDRPs. Chemically-mediated synaptic transmission was found to be necessary for the production of sDRPs because the addition of Mn2+ or Mg2+ ions or tetrodotoxin to the Ringer's solution or reduction of its Na+ concentration blocked sDRPs, whereas application of 4-aminopyridine enhanced them. It did not seem that a direct action of GABA on afferent fiber terminals was responsible for the generation of spontaneous potentials since an increase in sDRPs was seen after: application of the GABA antagonists, bicuculline and picrotoxin; exposure to the glutamic acid decarboxylase inhibitor, semicarbazide (which significantly reduced the concentration of GABA in the cord); and lowering of the external Cl- concentration. Similarly taurine is probably not significant since the taurine antagonist, TAG, increased the amount of spontaneous activity. On the other hand, (--)-baclofen, which is thought to reduce excitatory amino acid release, D,L-alpha-aminoadipic acid, alpha, epsilon-diaminopimelic acid, and 2-amino-4-phosphonobutyric acid, which are believed to be selective postsynaptic excitatory amino acid antagonists, and [D-Pro2-D-Phe7-D-Trp9]-substance P, a postsynaptic blocker of the action of substance P, markedly and reversibly reduced sDRPs. Experiments were performed on isolated cords without supraspinal or afferent input; therefore sDRPs must be generated by intraspinal structures. It would seem that interneurons are responsible because addition of mephenesin or pentobarbital--compounds which inhibit polysynaptic reflex transmission involving interneurons--reduced the production of sDRPs. sDRPs may result from the action of excitatory transmitters such as L-glutamate, L-aspartate, or substance P released by interneuronal firing in the spinal cord. Moreover, because sDRPs were increased by application of yohimbine, corynanthine and propanolol and reduced by haloperidol, such interneurons may be under descending control of adrenergic and dopaminergic fibers.
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PMID:Spontaneous dorsal root potentials arise from interneuronal activity in the isolated frog spinal cord. 620 11

The nature of the putative transmitter(s) mediating the non-cholinergic excitatory post-synaptic potential (e.p.s.p.) described in the preceding paper was investigated by means of electrophysiological, pharmacological and immunohistochemical methods. Serotonin (1-10 microM) when applied by superfusion caused a slow depolarization that closely mimicked the synaptic response in about 60% of the coeliac neurones that exhibited a non-cholinergic e.p.s.p. The serotonin depolarization evoked in low-Ca2+, high-Mg2+ solution or in a Krebs solution containing cholinergic antagonists was quantitatively similar to that elicited in normal Krebs solution. When compared in the same neurones the membrane resistance change during the course of the serotonin depolarization and of the non-cholinergic e.p.s.p., as well as their respective responses to conditioning polarization, were similar. The non-cholinergic e.p.s.p. was reversibly abolished during serotonin-induced depolarization; the blockade persisted when the membrane potential was restored to the resting level by hyperpolarizing current. The serotonin depolarization as well as the non-cholinergic e.p.s.p. were reversibly suppressed by cyproheptadine (20-50 microM), a serotonin antagonist, and enhanced by fluoxetine (30-50 microM), a serotonin reuptake inhibitor. On the other hand, pre-treating the ganglia with L-tryptophan (50 microM), a precursor of serotonin, preferentially augmented the synaptically induced response. A portion of the neurones (15%) were depolarized by substance P (1 microM) which also reversibly desensitized the non-cholinergic e.p.s.p. elicited in these neurones. The remaining neurones (25%) were insensitive to either serotonin or substance P, and the non-cholinergic e.p.s.p.s elicited in these cells were likewise not appreciably affected by these two agents. Furthermore, cyproheptadine, fluoxetine and L-tryptophan had no significant effect on the non-cholinergic e.p.s.p.s elicited in serotonin-insensitive neurones. Using the immunohistofluorescent techniques, dense but unevenly distributed serotonin immunoreactive nerve fibres could be observed surrounding many coeliac neurones. Immunoreactivity was not observed in the ganglia incubated with antisera pre-absorbed with excess serotonin. Collectively our results suggest that serotonin is the mediator of non-cholinergic e.p.s.p.s. elicited in about 60% of coeliac neurones sampled in this study, and that in the remaining neurones the slow depolarization may be generated by substance P and/or some unknown transmitter(s).
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PMID:Evidence for a serotonin-mediated slow excitatory potential in the guinea-pig coeliac ganglia. 620 46

In the presence of extracellular Ca2+, 6,7-dihydro-6,8,8, 10-tetramethyl-8H-pyrano [3, 2-g] chromone-2-carboxylic acid (EAA) had an inhibitory effect on the substance P-induced histamine release from rat peritoneal mast cells. Not only Ca2+ but also Mg2+, Sr2+ and Ba2+ were effective in enhancing the activity of EAA. Marked tachyphylaxis to EAA developed irrespective of the presence or absence of extracellular Ca2+. Cross-tachyphylaxis was observed between EAA and disodium cromoglycate (DSCG). These results indicate that the mode of action of EAA is similar, but not identical, with that of DSCG.
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PMID:The inhibition of substance P-induced histamine release from mast cells by 6, 7-dihydro-6, 8, 8, 10-tetramethyl-8H-pyrano-[3, 2-g] chromone-2-carboxylic acid (EAA). 620 53

1. The depressant actions of Mg2+ and a range of other divalent ions on synaptic excitation and on responses produced by excitatory amino acids and other putative transmitters have been investigated in hemisected isolated spinal cords of frogs and neonatal rats. Some comparative studies were also made using the rat isolated superior cervical ganglion. 2. At concentrations above 10 microM, Mg2+ selectively antagonized N-methyl-D-aspartate (NMDA)-induced motoneurone depolarization as recorded from ventral roots of tetrodotoxin-blocked spinal cords. Depolarization evoked by quisqualate (unaffected by 20 mM-Mg2+) was resistant to the depressant action of these ions, while depolarizations evoked by other excitant amino acids were depressed to intermediate degrees. 3. Mn2+, Co2+ and Ni2+ had qualitatively similar actions to Mg2+; Mn2+ was somewhat less potent and Co2+ and Ni2+ more potent than Mg2+. The alkaline earth metal ions, Ca2+, Sr2+ and Ba2+, had very weak Mg2+-like actions. Ca2+ and Mg2+ acted additively in depressing amino acid-induced responses. 4. Mg2+ also depressed motoneurone responses evoked by noradrenaline, substance P and carbachol in the neonatal rat isolated spinal cord. However, none of these effects were as marked as the depression of NMDA-induced responses by Mg2+ in this preparation. Mg2+ did not depress motoneurone depolarization produced by 5-HT in the rat spinal cord or the depolarizing action of GABA on primary afferent terminals of the isolated frog spinal cord. 5. At concentrations producing marked depression of NMDA-induced responses, Mg2+ also depressed synaptic transmission in spinal cords in the absence of an effect on ganglionic transmission. At the same concentrations, Mn2+, Co2+ and Ni2+ depressed synaptic transmission in both preparations. 6. From the similarity in action between Mg2+ and the D-alpha-aminoadipate group of NMDA antagonists, it is suggested that the central depressant action of low concentrations of Mg2+ involves predominantly a postsynaptically mediated interference with the action of an excitatory amino acid transmitter.
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PMID:Selective depression of excitatory amino acid induced depolarizations by magnesium ions in isolated spinal cord preparations. 625 39

To study further the ongoing spike discharge of burst-type myenteric neurons, extracellular recordings were made with either Teflon-insulated Pt wire electrodes (tip diam, 20 micrometers) or 3 M NaCl-filled glass micropipettes (tip diam, 1-2 micrometers). Presynaptic fibers to the erratic bursters were activated by electrical shocks delivered through Teflon-insulated Pt wire electrodes. Single electrical shocks applied to either the surface of the ganglion or an interganglionic connective elicited bursts of spikes that had parameters (interspike intervals and spikes per burst) that closely resembled the spontaneously occurring bursts in the same neuron. The latencies of the responses to electrical stimulation ranged from 5 to 30 ms. The responses were reversibly abolished when the concentration of Mg2+ in the bathing solution was elevated to 12 mM. The responses to electrical stimulation were unaffected by atropine, hexamethonium, d-tubocurarine, epinephrine, norepinephrine, methysergide, morphine, naloxone, and substance P. The ongoing burst-type discharge of cat myenteric neurons appeared to reflect a synaptic event that could be mimicked by electrical stimulation of presynaptic fibers. The identity of the neurotransmitter that elicits the burst-type discharge is unknown. The transmitter is probably not acetylcholine, serotonin, norepinephrine, an opiatelike peptide, nor substance P.
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PMID:Synaptic activation of erratic burst-type myenteric neurons in cat small intestine. 724 44


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